human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

s and other

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

s, the adrenocortical hormones are

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s produced by the adrenal cortex, the outer region of the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

. These polycyclic steroid hormones have a variety of roles that are crucial for the body's response to stress (for example, the fight-or-flight response), and they also regulate other functions in the body. Threats to

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

, such as

injury Injury is physiological damage to the living tissue of any organism, whether in humans, in other animals, or in plants. Injuries can be caused in many ways, including mechanically with penetration by sharp objects such as teeth or with ...

, chemical imbalances,

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

, or

psychological stress In psychology, stress is a feeling of emotional strain and pressure. Stress is a form of psychological and mental discomfort. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the envi ...

, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

and

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

. These hormones also function in regulating the conservation of water by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s and glucose metabolism, respectively.Genest, J., Biron, P., Koiw, E., Nowaczynski, W., Chretien, M., & Boucher, R. (1961). Adrenocortical hormones in human hypertension and their relation to angiotensin. Circulation Research, 9, 775-791.

Classes

Adrenocortical hormones are divided into three classes by function: mineralocorticoids, glucocorticoids, and androgens. # Mineralocorticoid hormones are synthesized in the outermost layer of the adrenal cortex known as the zona glomerulosa.Shier, D., Butler, J., Lewis, R. “Adrenal Glands.” Hole’s Human Anatomy & Physiology. 12th ed. New York: McGraw-Hill, 2010. 504-508. Their function is to regulate the concentration of electrolytes circulating in the blood. For example,

functions to raise blood sodium levels and lower blood potassium levels by targeting the kidneys. Specifically, it binds receptors of cells that comprise the distal tubules of the kidneys which then stimulate

ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...

to conserve sodium and excrete potassium. onnell, J. M. C., & Davies, E. (2005). The new biology of aldosterone. Journal of Endocrinology, 186, 1-20./ref> Additionally, the ion gradient initiates conservation of water. # The

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

family of hormones is synthesized in the middle layer of the adrenal cortex known as the zona fasciculata. These hormones regulate the processing of proteins, fats, and carbohydrates by the human body. They also play a role in maintaining a normal stress response cycle. # Androgens, or sex hormones, are synthesized in the innermost layer of the adrenal cortex known as the zona reticularis. These hormones, such as

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

in females and

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

in males, are commonly known for promoting sexual characteristics and the maturation of reproductive organs of the respective gender.

Structure

Adrenocortical hormones are considered steroid hormones because of the shared characteristic of a

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

backbone. The structures of different steroids differ by the types and locations of additional atoms on a

backbone.Nelson, D. L., Lehninger, A. L., and Cox, M. M. “Hormones are Chemically Diverse.” Lehninger Principles of Biochemistry. 6th ed. New York: W.H. Freeman, 2013. 908. The

backbone consists of four

hydrocarbon In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and Hydrophobe, hydrophobic; their odor is usually fain ...

rings, three

cyclohexane Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colourless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclohexan ...

rings and one cyclopentane, that contribute to its insolubility in aqueous environments. However, the

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

nature allows them to readily diffuse through the plasma membrane of cells. This is important to the function of steroid hormones as they rely on cellular response pathways to restore the homeostatic imbalance that initiated the hormone release.

Synthesis

The synthesis of adrenocortical steroid hormones involves a chain of oxidation-reduction reactions catalyzed by a series of enzymes. Synthesis begins with a molecule of

. Through shared intermediates and pathways branching off those shared intermediates, the different classes of steroids are synthesized. Steroids are synthesized from

in their respective regions of the adrenal cortex. The process is controlled by steroidogenic acute regulatory protein (StAR) which sits in the mitochondrial membrane and regulates the passage of

. This is the rate-limiting step of steroid biosynthesis. Once StAR has transported

into the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, the

molecule undergoes a string of oxidation-reduction reactions catalyzed by a series of enzymes from the family of

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzymes. A

coenzyme A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can ...

system called adrenodoxin reductase transfers electrons to the P450 enzyme which initiates the oxidation-reduction reactions that transform

into the steroid hormones.Sushko, T. A., Gilep, A. A., & Usanov, S. A. (2012) Mechanism of intermolecular interactions of microsomal cytochrome P450s CYP17 and CYP21 involved in steroid hormone biosynthesis. Biochemistry, 77(6), 585-592. Though synthesis is initiated inside

, precursors are shuttled to the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

for processing by enzymes present in the

. The precursors are shuttled back to the

in the region of the adrenal cortex within which synthesis initially began and it is there that synthesis is completed.Duarte, A., Poderoso, C., Cooke, M., Soria, G., Cornejo Maciel, F., et al. (2012). Mitochondrial fusion is essential for steroid biosynthesis. PLoS ONE, 7(9): e45829.

Pathology

Cushing's Syndrome

Cushing's syndrome arises from the repeated hypersecretion of glucocorticoids. It can be caused by either an adrenal tumor or by hypersecretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. It is predominantly due to an excess of the

. Secretion is typically regulated by the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

which secretes corticotropin-releasing hormone (CRH) to the

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

, stimulating the pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH then travels to the adrenal glands and induces the release of

into the bloodstream.Porterfield, J. R., Thompson, G. B., Young, W. F., et al. (2008). Surgery for cushing’s syndrome: An historical review and recent ten-year experience. World J. Surg., 32, 659-677. In Cushing's syndrome, this process occurs in excess. Some symptoms of an individual with Cushing's syndrome include low tissue protein levels, due to muscle and bone atrophy, and high blood glucose levels. Sodium levels also see an increase which results in fluid retention in tissues and elevated blood pressure. In addition to hypersecretion of

, excess androgens are secreted.Low, G., & Sahi, K. (2012). Clinical and imaging overview of functional adrenal neoplasms. International Journal of Urology, 19, 697-708. In females, increased secretion of androgens, such as

, results in masculinization which may present as facial hair growth and a deepened voice. Treatment for Cushing's syndrome aims to reduce the high levels of

circulating through the human body. The course of action ultimately depends on the cause of the hypersecretion. Cushing's can be induced by repeated synthetic steroid use to treat inflammatory diseases, or it can also be caused by a tumor in the

. In either case, treatment may rely on removal of the tumor or of the adrenal glands. Without the adrenal glands, the human body is unable to supply the hormones it produces and therefore requires hormone replacement therapy.

Addison's Disease

Addison's disease is an autoimmune disorder that affects the adrenal cortex such that it is unable to efficiently secrete hormones. The immune system specifically targets the cells of the adrenal cortex and destroys them, but Addison's disease can also be caused by a severe infection such as

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

. Some symptoms include

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

and decreased blood sodium levels and increased blood potassium levels caused by a deficiency of

. These electrolyte imbalances induce nerve and muscle issues. Other symptoms include fatigue, salt cravings, weight loss, and increased skin pigmentation. Increased skin pigmentation is caused by a deficiency of the adrenocortical hormone hydrocortisone. Its normal behavior would be as

negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...

at the

, stimulating the

to decrease secretion of corticotropin. Because hydrocortisone is not able to be produced in Addison's disease, the

continues to secrete corticotropin which binds to the receptor for

melanocyte-stimulating hormone The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating ...

. It then causes

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...

to produce more pigment, thus darkening the skin tone.Winqvist, O., Rorsman, F., & Kampe, O. (2000). Autoimmune adrenal insufficiency. BioDrugs, 13(2), 107-114. The standard treatment for Addison's disease is hormone replacement therapy for the mineralocorticoids and glucocorticoids that are no longer able to be synthesized. 2Former U.S. President John F. Kennedy is a well-known individual who suffered from Addison's disease throughout his presidency. Due to the availability of hormone replacement therapy, he and his staff were able to cover up his condition.

Stress and immunity

Recent studies have discovered a pathway that links stress to the onset of disease through the activation of certain genes.Cole, J.T., Mitala, C. M., Kundu, S., Verma, A., Elkind, J.A., Nissim, I., & Cohen, A.S. (2010). Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proceedings of the National Academy of Sciences, 107, 366-371. The experience of psychological stress activates transcription factors that activate genes. In a study by Cole et al., it was concluded that GABA-1 transcription factor activates the interleukin-6-gene. This gene codes for a protein that activates the inflammatory response which directs an immune response to the site of the inflammation. Chronic inflammation makes an individual more susceptible to diseases such as

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...

, and

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

. Another study found that physical stress caused increased

: DHEAS (dehydroepiandrosterone sulphate) molar ratios which may contribute to reduced immunity, especially in the elderly for whom

: DHEAS ratios are already increased. This is because DHEAS levels decrease with age while

levels do not. This high ratio was found to suppress the activity of neutrophils and raise susceptibility for

.Butcher, S. K., Killampalli, V., Lascelles, D., Wang, K., Alpar, E. K., & Lord, J. M. (2005). Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging Cell, 4, 319-324.

References

{{Authority control Hormones